β-Caryophyllene from Chilli Pepper Inhibits the Proliferation of Non-Small Cell Lung Cancer Cells by Affecting miR-659-3p-Targeted Sphingosine Kinase 1 (SphK1)

BACKGROUND: β-Caryophyllene is the main ingredient of chilli pepper and used for the prevention of various cancers, while the molecular mechanism for its effects on non-small cell lung cancer (NSCLC) remains unclear. METHODS: NSCLC cell lines A549 and NCI-H1299 were treated with β-Caryophyllene and miR-659-3p (a potential tumor suppressor) mimic or siRNA. The levels of miR-659-3p, sphingosine kinase 1 (SphK1), apoptotic factors and oxidative stress factors were investigated. RESULTS: β-Caryophyllene inhibited NSCLC growth, promoted their apoptotic rate, increased the level of miR-659-3p, apoptotic factors (cleaved caspase-3 and BAX), antioxidant factors (SOD, CAT and GPx) and reduced the level of oxidative stress (ROS and NO) and SphK1. miR-659-3p mimic and siRNA affected NSCLC growth, their apoptosis, and biochemical indices. CONCLUSION: β-Caryophyllene of chilli pepper exerts inhibitory activity in NSCLC cells possibly by affecting miR-659-3p-targeted SphK1.